Each year approximately 16,000 new adult brain tumors are diagnosed in the United States (see, e.g., P. Y. Wen, S. Kesari, N Engl J Med 359, 492 (Jul. 31, 2008)). Cytoreduction, verification of histology, and identification of tumor invasion in macroscopically normal-appearing tissue are crucial to predict prognosis (see, e.g., M. Lacroix et al., J Neurosurg 95, 190 (August, 2001)). Unlike in other organ systems, complete resection of cancer in the brain is often not possible because of tumor cell infiltration and the goal to preserve brain tissue. Furthermore, discerning among gliosis, radiation effects, and tumor-containing tissue after a recurrence can be difficult. The current neurosurgical armamentarium for guiding tumor resection is based on macroscopic identification of tumor region and does not result in complete resection and clearance of surgical margins. Frozen sections are time-consuming and often do not reveal the histologic features needed for final diagnosis when compared with permanent sections. An optimal imaging technique would allow intraoperative identification of regions containing tumor and their microscopic extent, producing real-time data that enhances ongoing surgical decisions without significantly prolonging anesthesia and operative times.
Fluorescence imaging approaches to these challenges have been developed. 5-aminolevulinic acid is used for visible wavelength fluorescence (VWF) imaging at operating microscope magnification during glioma surgery (see, e.g., W. Stummer et al., The Lancet Oncology 7, 392 (2006)).